Heart valve disease is a common degenerative condition that compromises physiologic function and causes limiting symptoms and threat to life in millions of patients all over the world. There are various underlying causes, but malfunction of heart valves is ultimately expressed as insufficient conduction of blood through the plane of the valve due to narrowing of the anatomic pathway (stenosis), or as incompetent closure that allows blood to return back through the valve again, thereby reducing the effective forward conduction of blood through the valve (insufficiency or regurgitation). These hemodynamic states lead to 1) deficiency of cardiac output and 2) adverse loads on the pumping chambers of the heart, both of which in turn lead to functional compromise of the patient and often premature death unless effectively corrected.
Definitive corrective treatment of heart valve disease is conventionally performed by open-chest surgical techniques, wherein the valve is manipulated, repaired, or replaced with a prosthetic valve under direct vision. Heart valve surgery is performed in hundreds of thousands of cases yearly world-wide, but carries a high burden of cost, morbidity, and mortality, especially in susceptible patients who may be elderly or otherwise physiologically compromised by collateral disease. Further, the costs and resource requirements of the surgical enterprise restrict the availability of heart valve replacement to many more patients all over the world.
In pursuit of alternatives to heart valve surgery, over the last ten years a number of development programs have brought percutaneous, trans-catheter implantation of prosthetic heart valves into commercial use in the European Union (EU) and into pivotal clinical trials in the United States of America. Initial clinical experience in the EU was directed toward patients who had critical aortic valve stenosis, but were deemed to be at unacceptably high risk for open-heart surgical valve replacement. In several thousand such cases, utilizing both balloon-expandable and self-expanding designs in two separate programs, percutaneous heart valve replacement (PHVR) was shown to be feasible and possibly competitive with surgery in selected patients with 12-18 month mortality rates of about 25%. Grube E., et al., Progress and Current Status of Percutaneous Aortic Valve Replacement: Results of Three Device Generations of the CoreValve Revalving System, Circ. Cardiovasc Intervent. 2008; 1:167-175.
The application of PHVR thus far has been challenged by the technical difficulties of the implantation sequence—especially in the aortic valve position. The technique for available devices is limited by the large caliber of the devices and their delivery catheters; often, if it can be done at all in some smaller arteries, open surgical exposure and management of the femoral artery is required to insert the 18-24 French (6-8 mm diameter) systems, and their bulkiness inside the central arteries can threaten the safety of the delivery sequence. Further, access site bleeding complications form a significant part of the adverse events of the procedures.
Typically, the current PHV designs comprise a biological membrane forming the operating leaflets of the valve, attached within a metal frame, that is then collapsed onto a delivery catheter or balloon, and then constrained within an outer sheath. After an initial dilation of the diseased valve with a large balloon, this assembly is then advanced to the plane of the valve and deployed by self-expansion or by balloon expansion.
The effective caliber of the valve delivery system is determined by the total bulk of each coaxially mounted component. The bulk of the PHV itself is determined by the diameter of the frame and by the thickness, stiffness, and particular arrangement of the inner membrane forming the operating leaflets of the valve. The characteristic thickness of current PHV membranes is thus a limiting factor in the ultimate delivery profile of the PHV. Such characteristic membrane thickness is, in turn, a result of the methods by which it is processed and ultimately delivered for use. Typically, glutaraldehyde fixation (for protein cross-linking) of animal tissue is employed to produce suitable biological membranes for incorporation. Requirements for strength and durability have determined the most useful ranges for tissue thickness and cross-linking while typically imposing countervailing stiffness and brittleness. Subsequent hydration in suitable solutions improves these characteristics, but the hydrated membrane by this means also gains thickness.
One of the evident requirements for a PHV design is that the valve functions with a high degree of competence immediately on deployment, since the patient's hemodynamic survival depends on it. To this end, in part, like surgical valve prostheses, current PHV designs are completed, transported, and delivered for use in a hydrated state in a jar of solution. In use, commercially available surgical and percutaneously implanted bioprosthetic heart valves are rinsed and prepared before use in a “wet” state. More particularly, commercially available prosthetic heart valves are rinsed, crimped, and mounted in the catheterization lab. Accordingly, problems with current commercially available prosthetic heart valves include the time, cost and variability associated with the necessity to rinse, crimp, and mount the valve in the catheterization lab. That is, current mounting of prosthetic heart valves in the catheterization lab imposes one or more of delay, cost, technical burdens and possible errors. Avoiding one or more of these problems would be advantageous. In addition, current “wet” valve designs impose additional profile on the collapsed valve. The hydrated membrane, while having desirable and necessary flexibility for reliable operation immediately on deployment, also imposes a large part of the thickness of the assembled and mounted valve that compromises its deliverability.
Expanding on some of the problems described above, the use of current PHVs in the catheter lab requires a number of preparatory acts that are potentially troublesome and can prolong the delivery sequence during a critical phase of the procedure. Since PHVs are delivered for use “wet” in a preservative solution, they have to be treated prior to insertion with a series of cleansing and hydrating solutions. Once this is completed, the PHVs have to be mounted on their delivery catheters. Special crimping and mounting tools are needed in the case of the balloon-expandable Edwards Sapien valve, for example. Accordingly, there is a need to address the shortcomings discussed above.